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Using a novel immunoassay, researchers were able to detect low levels of neurofilament light chain (NfL) in patients with progressive multiple sclerosis (MS). They propose that NfL could be used as a marker of disease progression and response to treatment.

LOS ANGELES — Evidence is growing that neurofilament light chain (NfL) protein in the blood could give crucial insights into the disease status in multiple sclerosis patients, along with information about response to treatment and progression prospects, an expert said here at the Hot Topics Plenary at the AAN Annual Meeting in late April.

The new marker could help improve patient care by helping clinicians navigate difficult decisions when there is a variety of therapeutic options to work with, said Jens Kuhle, MD, head of the MS Center at the University Hospital of Basel in Switzerland.

“We are facing significant challenges in treating and counseling our MS patients,” he said. “In relapsing remitting MS, there are plenty of treatments available. Sequencing drugs isn't easy in clinical practice at all. For monitoring efficacy of these treatments, we mostly rely on imaging studies that are constantly improving but can also fail for the individual patient.”

In progressive MS, in which few treatments are available, he said, “the process of developing new treatments could be facilitated by more convenient and more precise biomarkers.”

Neurofilament light chain in the cerebrospinal fluid is known to reflect neuronal damage, but the amount of NfL in the blood has been too low for assays to detect it.

“The limiting factor over many years was really that the levels in blood are approximately 50- to 100-fold lower than in the cerebrospinal fluid,” Dr. Kuhle said.

With the single molecule array immunoassay — a bead-based assay in which individual immunocomplexes sit in tiny wells — neurofilament light chain can be detected at much lower levels.

Using this technique, researchers examined data from the FREEDOMS and TRANSFORMS trials on the immunomodulator fingolimod. They reported in an abstract at the 2017 AAN Annual Meeting that NfL protein was elevated in MS patients compared to controls, and that NfL levels correlated with T2 and contrast enhancing lesion volume at baseline.

“There is a high correlation between CSF and blood NfL measures,” said Dr. Kuhle. “Blood NfL levels are increased in all stages of MS versus controls and blood NfL levels show a consistent association with clinical and MRI disease activity.”

Looking at data from those trials in a different way, researchers found significant decreases in blood NfL levels in those treated with fingolimod, compared to treatment with interferon-beta, he said.

“NfL is a marker of therapy response on the group level,” Dr. Kuhle said. “And the challenge at the moment is really to establish cut-offs for individual decision-making. This is what people are working on, but this also depends a lot on assay analytics and assay validation.”

Researchers are now even finding that levels of blood NfL can predict how much a patient's disease is likely to progress, with higher baseline levels associated with higher numbers of new T2 lesions, worse relapse rates, greater degrees of brain atrophy, and shorter times to disability milestones, Dr. Kuhle said.

In the future, patients may be able to be stratified in risk according to levels of NfL found in the blood, he said.

“A patient with a NfL level, age-corrected, above the 97.5 percentile has a clearly significantly higher risk of experiencing relapses over the next one or two years,” Dr. Kuhle said. “He has a two-fold odds of EDSS (Expanded Disability Status Scale) worsening in the next year. And he has additional reduction of brain volume over two and five years. And he has an additional significant risk of losing spinal cord volume over the next five years.”

In progressive MS, in which few treatments are available, he said, “the process of developing new treatments could be facilitated by more convenient and more precise biomarkers.”

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